University of Leeds
Antimicrobial resistance is one of the biggest threats globally, causing an estimated 4.95 million deaths annually, as well as prolonged hospital stays, medical device failure, and unsustainable healthcare costs.
Antimicrobial Photodynamic Therapy (APDT) is a promising antibiotic-free infection control strategy, whereby exposure of a photosensitiser (PS) to a specific light source in the presence of molecular oxygen generates reactive oxygen species that are toxic to a broad range of pathogens. However, the fast diffusion of PS away of the infection site causes tissue staining and short-lived antimicrobial effect, which limit the clinical use of APDT. To address these challenges, this study explores the integration of a fibre-forming polymer system with on-demand antimicrobial effect, aiming to generate a photodynamic wound dressing through either dispersion or chemical binding of a PS.
Electrospun meshes were fabricated using biodegradable polyesters, e.g. poly[(rac-lactide)-co-(glycolide)], and methylene blue (MB), achieving >97 wt.% encapsulation efficiency. Significant E. coli reduction (≥ 1 log) and preserved fibroblast viability were observed after 30-60 min mesh exposure to white light, while at least 35 wt.% of MB was released following 48-hour mesh incubation in vitro. To achieve long-lasting APDT, we subsequently explored the chemical binding of an MB derivative, i.e. toluidine blue (TB). TB conjugation was confirmed via 1H-NMR, FTIR and UV-Vis spectroscopies, successfully yielding minimal release (< 1 wt.%) after 96-hour in vitro and complete eradication of P. aeruginosa following 60-min light exposure.
This study successfully demonstrates the encapsulation of a PS onto a biodegradable polymer system, aiming to accomplish photodynamic infection control that is safe, staining-free and tolerated by mammalian cells. This technology could be exploited for the development of advanced and sustainable antimicrobial wound dressings for chronic wound management.
Abstract
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